2020 Virtual AIChE Annual Meeting
(157z) Self-Assembled Cgamp-Sting?tm Signaling Complex As a Bioinspired Platform for Cgamp Delivery
Authors
He, Y. - Presenter, MIT
Hong, C., MIT
Yan, E., MIT
Fletcher, S., Massachusetts Institute of Technology
Zhu, G., Northeastern University
Yang, M., Northeastern University
Sun, X., Northeastern University
Li, Y., Synthetic Biological Center, MIT
Li, J., Massachusetts Institute of Technology
Irvine, D., MIT
Hammond, P. T., MIT
The stimulator of interferon (IFN) genes (STING) pathway constitutes a highly important part of immune responses against various cancers and infections. Consequently, administration of STING agonists such as cyclic GMP-AMP (cGAMP) has been identified as a promising approach to target these diseases. In cancer cells, STING signaling is frequently impaired by epigenetic silencing of STING; hence, conventional delivery of only its agonist cGAMP may be insufficient to trigger STING signaling. In this work, while expression of STING lacking the transmembrane (TM) domain is known to be unresponsive to STING agonists and is dominant negative when coexpressed with the full-length STING inside cells, we observed that the recombinant TM-deficient STING protein complexed with cGAMP could effectively trigger STING signaling when delivered in vitro and in vivo, including in STING-deficient cell lines. Thus, this bio-inspired method using TM-deficient STING may present a new and universally applicable platform for cGAMP delivery.